Saturday, Jun 5, 2004
New Orleans -- June 5, 2004 --Genentech, Inc. (NYSE: DNA), Biogen Idec Inc. (Nasdaq: BIIB) and Roche (SWX Zurich) today announced positive data from a large, randomized, Phase III cooperative group trial (E1496) evaluating Rituxan® (Rituximab), known as MabThera® in Europe, as maintenance therapy for newly diagnosed patients with indolent non-Hodgkin's lymphoma (NHL) following initial (induction) treatment with chemotherapy. The study authors concluded that there was a significant improvement in progression-free survival (PFS), the primary endpoint of the study. The authors estimated that 73 percent of patients who received Rituxan maintenance therapy were free of disease progression and alive at two years compared to 43 percent of patients who received no further treatment. In this trial, maintenance therapy began four weeks after the last cycle of chemotherapy and was defined as four doses of Rituxan (375 mg/m2) every six months for two years. PFS was defined as the time from randomization to the first documented disease progression or death. These data were highlighted in a press conference and will be presented today at the 40th Annual Meeting of the American Society of Clinical Oncology (ASCO).
"These data suggest the possibility of using Rituxan to treat indolent NHL as a chronic disease," said Gwen Fyfe, M.D., Genentech's vice president, Clinical Hematology/Oncology. "Patients with indolent NHL have a higher risk of multiple relapses and are likely to require ongoing treatment to keep their disease in remission. The toxicities associated with chemotherapy have prevented patients and physicians from actively keeping this disease in ongoing remission."
"We're very encouraged by the results of this study which add to the body of evidence showing that Rituxan maintenance therapy may be an important treatment option for patients with indolent lymphoma," said Burt Adelman, M.D., executive vice president, Development, Biogen Idec.
The Eastern Cooperative Oncology Group (ECOG) began enrollment to the study in 1998. It was stopped early in November 2003 after a pre-planned interim analysis revealed it had reached its pre-specified efficacy endpoint early. At that time, randomization to the observation arm of the study was halted. Of 401 previously untreated indolent NHL patients treated with CVP (cyclophosphamide, vincristine, prednisone) chemotherapy, 322 (305 evaluable) patients with a response (partial or complete) or stable disease following a maximum of eight doses of induction therapy with CVP were randomized to receive either Rituxan maintenance therapy or no additional treatment and were included in this analysis. No chemotherapy was administered to either treatment group after the induction phase of the study. According to the study authors, no significant increase in Grade 3 or 4 toxicities occurred in patients treated with Rituxan maintenance therapy.
"Earlier studies of maintenance therapy with Rituxan suggest this treatment approach may be a means of prolonging remissions in patients with indolent NHL," said Howard S. Hochster, M.D., Professor, NYU School of Medicine and the NYU Cancer Institute. "These results provide the first evidence from a randomized study that Rituxan maintenance therapy prolongs remissions following treatment with standard chemotherapy. Because the trial was stopped early, long-term follow-up will be necessary to determine if the prolonged remission achieved with Rituxan maintenance therapy translates into improved survival."
About Non-Hodgkin's Lymphoma
There are more than 300,000 people in the United States with B-cell NHL. Approximately 50 percent have indolent or follicular lymphoma, while the other half are patients with aggressive NHL. According to the American Cancer Society, more than 54,000 men and women in the United States are diagnosed each year with NHL.
Rituxan Safety Profile
Rituxan is generally well tolerated by patients. The majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include but are not limited to: flu-like fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema and hypotension. These symptoms vary in severity and generally are reversible with medical intervention. In rare instances, severe and fatal infusion-related reactions have occurred, nearly all of which have been associated with the first Rituxan infusion. These events appear as manifestations of an infusion-related complex and include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock and tumor lysis syndrome. Patients who develop clinically significant infusion-related cardiopulmonary events should have their Rituxan infusion discontinued and receive medical treatment.
In rare instances, severe mucocutaneous skin reactions have occurred that may be associated with Rituxan therapy. Many of these reactions have been described as paraneoplastic pemphigus and are known to be associated with various B-cell lymphomas, particularly NHL and chronic lymphocytic leukemia (CLL). Patients who develop a severe mucocutaneous skin reaction should have Rituxan discontinued and receive appropriate medical treatment including a skin biopsy to guide therapy.
Rituxan is a therapeutic antibody that binds to a particular protein -- the CD20 antigen -- on the surface of normal and malignant B-cells. It then recruits the body's natural defenses to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.
Rituxan is indicated as a single-agent treatment for relapsed or refractory low-grade or follicular, CD20-positive, B-cell NHL. More than 300,000 patients have been treated with Rituxan worldwide since approval.
Genentech and Biogen Idec co-market Rituxan in the United States. Roche markets Rituxan in the rest of the world, except Japan, where Rituxan is co-marketed by Roche, Chugai and Zenyaku Kogyo Co. Ltd.
The Eastern Cooperative Oncology Group (ECOG) is one of the largest clinical cancer research organizations in the United States. It conducts clinical trials in all types of adult cancers. ECOG was established in 1955 as one of the first cooperative groups launched to perform multi-center cancer clinical trials.
Genentech is committed to changing the way cancer is treated by establishing a broad oncology portfolio of innovative, targeted therapies with the goal of improving patients' lives. The company is the leading provider of anti-tumor therapeutics in the United States. Genentech is leading clinical development programs for Rituxan® (Rituximab), Herceptin® (Trastuzumab), and Avastin (bevacizumab) and markets all three products in the United States either alone (Avastin, which it recently launched in the United States, and Herceptin) or with Biogen Idec Inc. (Rituxan). Genentech has licensed Rituxan, Herceptin and Avastin to Roche for sale by the Roche Group outside of the United States.
The company has a robust pipeline of potential oncology therapies with a focus on four key areas: angiogenesis, apoptosis (i.e. programmed cell death), the HER pathway and B-cell biology. Potential oncology therapies directed at the HER pathway include Tarceva (erlotinib) and a therapeutic antibody currently in Phase II trials. Also in early development are a small molecule directed at the hedgehog pathway, a therapy targeting apoptosis and a humanized anti-CD20 antibody for hematology/oncology indications.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Eighteen of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes 13 biotechnology products directly in the United States. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange under the symbol DNA. For press releases and additional information about the company, please visit http://www.gene.com.
About Biogen Idec
Biogen Idec creates new standards of care in oncology and immunology. As a global leader in the development, manufacturing, and commercialization of novel therapies, Biogen Idec transforms scientific discoveries into advances in human healthcare. For product labeling, press releases and additional information about the company, please visit http://www.biogenidec.com.
Roche in Oncology
Within the last five years the Roche Group has become the world's leading provider of anti-cancer treatments, supportive care products and diagnostics. Its oncology business includes an unprecedented four marketed products with survival benefit: Herceptin, MabThera, Xeloda and Avastin (launched by Genentech in the US recently), which treat a range of malignancies such as breast cancer, non-Hodgkin's lymphoma and colorectal cancer. Other key products include NeoRecormon (anaemia in various cancer settings), Bondronat (prevention of skeletal events in breast cancer and bone metastases patients, hypercalcemia of malignancy), Kytril (chemotherapy and radiotherapy-induced nausea and vomiting) and Roferon-A (leukaemia, Kaposi's sarcoma, malignant melanoma, renal cell carcinoma). CERA is the most recent demonstration of the commitment to anaemia management. Roche's cancer medicines generated sales of more than 6 billion Swiss francs in 2003.
In a recent phase III study Tarceva met its primary endpoint of improving overall survival in patients with non-small cell lung cancer.
Roche is developing new tests, which will have a significant impact on disease management for cancer patients in the future. With a broad portfolio of tumor markers for prostate, colorectal, liver, ovarian, breast, stomach, pancreas and lung cancer, as well as a range of molecular oncology tests, we will continue to be the leaders in providing cancer focused treatments and diagnostics.
Roche Oncology has four research sites (two in the US, Germany and Japan) and four Headquarter Development sites (two in the US, UK and Switzerland).
For full prescribing information, including Boxed Warnings, please call 650-225-5873. For more information on Rituxan, visit http://www.rituxan.com.